Is CTF1 p.Val104Ala (c.311T>C) pathogenic?

CTF1 p.Val104Ala (c.311T>C) is classified Uncertain significance in CTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: ambiguous (0.4469); Very rare (popmax 0.00196%, nfe).

How common is CTF1 p.Val104Ala (c.311T>C) in the general population?

CTF1 p.Val104Ala (c.311T>C) is very rare (popmax 0.00196%, nfe) (gnomAD).

What do computational predictors say about CTF1 p.Val104Ala (c.311T>C)?

AlphaMissense predicts ambiguous (score 0.4469) — an in-silico prediction, not a clinical call.

CTF1 p.Val104Ala

c.311T>C · rs1367415789 · VCV1356394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4469	ambiguous
REVEL	0.392	indeterminate
SaProt	LLR -7.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,892 bp · p 0.33 · regional, not allelic
Overall
CADD	17.55	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00196% European (non-Finnish) · 18/920,028 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00101%

Overall 0.00185% 18/973,724 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTF1
Protein: p.Val104Ala
Coding: c.311T>C
MANE Select: NM_001330
dbSNP: rs1367415789
Type: single nucleotide variant
Location: chr16:30902244 (GRCh38)
Gene constraint: LOEUF 1.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.94

Full CTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTF1 c.*5C>A Uncertain significance ★★ same type
CTF1 p.Ala156Thr Uncertain significance ★★ ⚠ same type
CTF1 p.Ala34Val Uncertain significance ★★ ⚠ same type
CTF1 p.Arg107Ser Uncertain significance ★★ ⚠ same type
CTF1 p.Arg176His Uncertain significance ★★ ⚠ same type
CTF1 p.Arg65Gln Uncertain significance ★★ ⚠ same type
CTF1 p.Asp191Glu Uncertain significance ★★ ⚠ same type
CTF1 p.Asp54Glu Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctf1-p-val104ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown